Project - Pathogenic pathways of copper deficiency in Parkinson’s disease

Disease area:

Parkinson’s disease

Research Project Aims

• To quantify the proportions of differentially metallated SOD1 species in post-mortem Parkinson’s disease brains;
• To identify the presence of atypical post-translational modifications to SOD1 protein in post-mortem Parkinson’s disease brains;
• To characterise the hSOD1^WT/mCtr1^+/- mouse model, and validate whether it demonstrates neuronal loss and SOD1 pathology.

Research Project Description

Parkinson’s disease is the most common neurodegenerative movement disorder that results from the death of a specific group of neurons in the brain. Whilst current our understanding of neuronal vulnerability is limited based, our findings strongly suggest that biometals are key players in initiating and propagating the neurodegenerative cascade in that region. A recent promising discovery by our research group demonstrated the abnormal misfolding and aggregation of a copper-dependent protein known as superoxide dismutase 1 (SOD1). In disease state, this aberrant protein is abundantly deposited in vulnerable brain regions characterised by neuronal loss, and a copper deficient environment. We have since developed a novel mouse model of Parkinson’s disease that recapitulates these features to investigate tractable treatments that may slow, or halt the disease process.